Stereoselective syntheses of nitrogen-containing chiral molecules for specific interactions with biological targets.

The design of small organic molecules derived from natural products is a main issue in organic chemistry, aimed to discover new potentially interesting bioactive compounds. New scaffolds for the stereoselective synthesis of diversely functionalized chiral enantiopure quinolizidines, indolizidines, lemhizidines and pyrrolizidines were synthesized from the cross- and ring closing-metathesis reactions of appropriate intermediates, readily available from L-pyroglutamic acid or by enzymatic desymmetrization.The versatility of this strategy was demonstrated by the synthesis of indolizidine, quinolizidine and pyrrolizidine-based azasugar analogues and of the natural alkaloids (+)-monomorine and lemhizidine 275A. The use of conformationally constrained scaffolds for the preparation of reverse turn mimics is another main topic in medicinal chemistry. A new proline-based spirotricyclic lactam is reported as an efficient type II’ ß-turn inducing peptidomimetic. After investigation of the reverse turn properties by computational techniques, the scaffold has been synthesized by a straightforward sequence relying on a key RCM reaction for the construction of the spirocyclic lactams ring. For its conformational properties the scaffold can be considered a privileged structure to be employed as a mimic of the ß-turn motif of the potent antibiotic Gramicidin S.